This invention concerns sterility in pharmacy procedures, and more particularly the invention is directed to sample testing of intravenous liquid filtering equipment, to determine whether the solution or mixture, prior to filtering, was actually sterile. The invention is directed specifically at situations wherein the usual visual test of the filter, by addition of growth medium to the upstream side of the filter followed by an incubation period, is ineffective because of turbidity of the IV fluid itself.
The problem addressed by the invention involves intravenous injection of either TNA (total nutrient admixtures), antibodies or any medicine that is injected into a patient intravenously, either for a short term in the hospital or over a longer term. This relates to a technique which has been used for some time, the use of an in-line filter in a tube positioned below an IV solution source, for filtration prior to IV injection. The object is to filter out any microbes which might be contained in the IV fluid, directing the filtrate into a sterile IV bag or bottle, then, when the filtration procedure is complete, to check as to whether the procedures used by the medical personnel were aseptic. This filtering and testing normally take place in the pharmacy. The filtered solution goes into a sterile IV container which is used for the actual IV administration. The test is conducted, after filtering is complete, by introducing into the upstream filter housing a growth medium which is supposed to be universal for many types of bacterial microbes as well as fungus, yeast, etc. The growth medium is clear and, after hours or days the microbes, if present, will feed on the growth medium and produce turbidity or cloudiness in an otherwise clear solution.
Regarding the prevalence of this testing, some pharmacies are very diligent about following the procedure of testing their IV admixtures and some pharmacies do no testing at all.
A problem arises with the increasing use of emulsions in IV liquids injected into the patient. TNAs by nature include emulsions and are cloudy. When a filtering procedure is complete using TNAs or other emulsions which are cloudy, a residue is present upstream of the micropore filter. If the growth medium is fed directly into this, it will be impossible to visually detect bacterial or other microbe growth because of the existing cloudiness.
Other tests for culture growth, in the face of this turbidity, are possible but not thorough.
Principal attempts at solving this problem are discussed in the article "Method for Testing the Sterility of Total Nutrient Admixtures" by J. W. Levchuk et al., Vol. 45, June 1988 American Journal of Hospital Pharmacy. These have included rinsing techniques with enzymes and surfactants which do help move some of the emulsion particles through the filter, but as concluded in the article, so much repeated rinsing is needed that it is not worthwhile to use these techniques, considering the time and expense involved.
Patents which address the issue of removing filtered materials from micropore filters in a medical environment, for various purposes, include Bush U.S. Pat. No. 4,036,698 and Lemonnier U.S. Pat. 4,640,777. Both these references discuss rinsing of the upstream side of the micropore or membrane type filter for sterility testing. Generally speaking, quite a number of cleaning techniques for filters have been known, including scraping, high-velocity air/water jets, many back flushing strategies including backflushing with lateral removal, and the use of parallel filters with switching of each filter from filter cycle to purge cycle.
Further, it has been known to use air pressure to push remaining liquid material through a micropore filter, where the liquid being filtered is highly valuable. After a cycle of filtration through such a filter medium, a substantial volume of unfiltered liquid often remains on the upstream side of the filter, due to the very small pore size as well as effects of surface tension. One manufacturer's literature mentions that the "hold-up volume" for its filter product is 5 microliters, but that this can be lowered to 1/2 microliter with "air purge". Thus, air pressure has been used in this general context to "purge" the remaining valuable liquid through the filter, but not for the purpose of clearing the upstream side for sterility testing and not, so far as known to the applicant, to force emulsion particles through the filter.